Mind and Body
First-of-its-kind study finds a counterintuitive use for prescription CBD
"This is a large and unmet clinical need."
As of now, there are no scientifically approved treatments for cannabis use disorder, an issue for those fighting a dependence on the drug. The need is there: Studies indicate that 47 percent of people who quit using marijuana experience withdrawals, while other research suggests 9 percent of people who use marijuana will become dependent on it.
A solution, however, could be on the horizon. In a recent double-blind randomized controlled trial, researchers discovered that cannabidiol (CBD), a chemical compound found in cannabis, can actually help people quit.
The study team found that prescription-grade CBD moderately reduced cannabis intake and helped people abstain from using cannabis more than a placebo treatment. Prescription CBD is typically more than 16 times stronger than commercially available CBD.
"There are currently no safe and effective treatments available for prescription to help people with cannabis use problems," study co-author Tom Freeman, a psychopharmacology researcher at the University of Bath, tells Inverse. "This is a large and unmet clinical need and could help people to quit in an acceptable treatment format."
The findings were published Tuesday in the journal Lancet Psychiatry.
The experiment — To determine if CBD is safe and might help people with cannabis use disorder, researchers recruited 82 people diagnosed with the disorder with cases that were considered at least moderately severe.
This means they experienced at least four out of 11 possible symptoms of addiction, including:
- Continued substance use despite having a persistent or recurrent social or interpersonal problem caused or exacerbated by the effects of the substance
- A great deal of time spent in activities necessary to obtain the substance, use the substance, or recover from effects.
"Most people who use cannabis do so without significant problems," Freeman explains. "Others find that it has a substantial negative impact on their life such as their ability to work, relationships with friends and family, and their mental and physical health."
The study participants recognized their cannabis use was interfering with optimal living and wanted to cut down on use. Each participant expressed the desire to quit the next month, cut marijuana with tobacco, and had tried to quit consuming cannabis on at least one occasion before.
Participants were randomly assigned to treatment groups and asked to take two capsules of prescription-grade CBD twice daily for four weeks. The placebo group was given sham capsules containing no CBD, while the others received a daily dose of either 200mg, 400mg or 800mg CBD.
All of the participants received six counseling sessions designed to help them quit using cannabis, which took place before and during the study period.
Throughout the study, researchers tested the participants urine weekly for THC to assess how much cannabis had been consumed in the past week. Participants were also asked to report how many days they had abstained from using cannabis that week.
Sham versus treatment — Early on in the study, researchers ruled out the 200-milligram condition as ineffective.
However, by the study's conclusion, daily CBD doses of 400 and 800 milligrams were both found to reduce participants’ cannabis intake. Specifically, these doses reduced THC levels in the urine by -94.21ng/mL and -72.02ng/mL, respectively.
People who took 400 to 800 milligrams of CBD were also more likely to abstain longer than the placebo group: The 400-milligram CBD group abstained half a day longer per week. The 800-milligram dose group had 0.3 days per week of extra abstinence. Both CBD doses worked better consumption and abstinence-wise than the placebo.
Throughout the study, participants didn't experience any severe adverse events related to consuming CBD. suggesting high quality, prescription CBD is relatively safe for use.
The future of CBD research — Studies haven't pinned down exactly why CBD seems to help people quit using marijuana. Previous research indicates that CBD can reduce cannabis cravings and may reduce mental health symptoms like anxiety, which in turn, influences use.
"CBD has contrasting and often opposite effects to THC on our endogenous cannabinoid systems," Freeman says. "In this way, CBD is very different from a nicotine patch or other replacement therapies."
THC, an active ingredient in marijuana that makes you "high," binds to specific brain receptors and influences reaction time, memory, and movement. CBD blocks the brain's receptors' from binding to cannabinoids, and may make people feel more relaxed. In theory, this process could also explain why CBD can be helpful — but more research is needed to be sure.
Freeman and his colleagues stress these findings shouldn't prompt people to run out and purchase CBD to "self-medicate" if they're trying to cut down on cannabis use.
CBD products sold without a prescription contain low doses of CBD — about 25 milligrams — and lack quality assurance, Freeman explains. Commercially available CBD products also have a variety of doses and sometimes contain THC. If you are looking for help, Freeman recommends you speak to a healthcare professional first.
Background: A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could o!er a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design.
Methods: We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-à-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36).
Findings: Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most e"cacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by –94·21 ng/mL (95% interval estimate –161·83 to –35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by –72·02 ng/mL (–135·47 to –19·52) and increased abstinence from cannabis by 0·27 days per week (–0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment.
Interpretation: In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use.